Diabetes Risk, on a Scale of 1 to 10

As a genre, personalized medicine has yet to deliver many individualized treatments. But progress has been more tangible on the diagnostics side.

Early warning: A technician examines a sample from a patient with prediabetes at Tethys Bioscience in Emeryville, CA.

Some of that progress has come from Tethys Bioscience, a startup in Emeryville, CA, that is working on tests for some of the country’s most prevalent diseases. Their first diagnostic, a blood test called PreDx, determines a person’s risk of developing diabetes over a five-year period. The test is already changing the way some physicians diagnose and treat their patients.

People with prediabetes don’t regulate blood sugar the way they should; of the 57 million or so people in the U.S. with this syndrome, only about 10 to 15 percent develop the full-blown disease. With proper diet and exercise, the trajectory toward diabetes can be slowed or even reversed. But the current standard for identifying diabetes risk, the fasting blood-glucose test, can’t determine which 10 to 15 percent are most likely to get the disease. As a result, doctors can’t easily figure out which patients to concentrate on.

There are a few tests to determine which patients are high-risk, but these tend to be expensive, resource-intensive, time-consuming, or all three. Tethys’s simple blood test, which costs $300 if patients pay out-of-pocket, can be almost as accurate.

“The PreDx risk score allows a physician to determine which subjects to focus their interventions on,” says Tethys president R. Michael Richey. Suddenly, a patient who might have once been told that his lab results indicate he’s on the verge of diabetes could be told the likelihood of disease progression as a percent. Someone else with similar fasting blood-glucose results might be told that if she doesn’t lose weight and start exercising, her risk of developing diabetes is quite high.

Richey and his colleagues at Tethys developed this “risk stratification” approach by hunting down blood-sample banks from long-term studies of large groups of patients with known health outcomes. The researchers tested these blood samples for as many potential diabetes markers as they could. Then they looked for protein combinations that differentiated those who developed full-blown diabetes from those who didn’t. “We ran them through complex algorithms and found the smallest number of markers that, when taken together, would accurately predict incidence of diabetes,” Richey says.

The resulting algorithm is based on seven proteins and metabolites present in blood. Tethys has tested this approach in two more large study groups with known diabetes outcomes, including a multi-ethnic U.S. population, and found the results to be just as accurate.

Such an advance in diagnostics is due to a convergence of new technology and disease-prevention research. “It’s a result of our understanding the human genome and better understanding the biology that leads to these metabolic disorders, as well as an enormous amount of research published that allowed us to understand which markers we need to look at,” he says. Tethys began marketing the test to physicians in 2008, and it’s been used at least 12,000 times since.

Patients receive their PreDx results in the form of a color-coded bar chart, with their risk level highlighted as green (low), yellow (moderate), or red (high), and a number between one and 10 (the higher the number, the greater their chance of developing diabetes). “The critical thing about the test is that you don’t need to be a rocket scientist to understand it, and that means that patients understand it and get motivated to really make changes,” says Ed Kersh, the chief of cardiology at St. Luke’s Hospital in San Francisco and a clinical professor of medicine at the University of California, San Francisco.

Kersh started using the test about a year ago, and he says the approach has led to healthy changes in weight and blood-glucose levels in over 90 percent of his high-risk patients. “Creating lifestyle change in patients is a very difficult thing–the success rate for diet, exercise, and smoking cessation is down around 10 percent unless they’re confronted with significant data,” he says.

One physician was so convinced by the PreDx methodology that he developed an entire weight-loss clinic around the concept of the PreDx test. Michael Abou Assaly directs the Health Living Clinic at the Great River Medical Center in Burlington, IA, and has used the test on about 750 patients. He’s seen significant lifestyle changes in about three-quarters of his high-risk patients (about 30 percent, he says). “It’s been like nothing I’ve ever seen, as far as a motivating tool,” Abou Assaly says.

Richard Bergman, a professor of physiology and biophysics at the Keck School of Medicine at the University of Southern California, specializes in diabetes risk prediction and has developed a clinical method that can measure that risk. But the PreDx test, he says, “is better than anything else you can do without a clinical test,” which requires time and money. “The fact that it can be measured from a blood sample and is much less labor-intensive means that it can be used routinely in a doctor’s office,” says Bergman, who is on the Tethy’s scientific advisory board.

Tethys hopes to submit its PreDx research to the FDA for approval sometime in 2011. (Such diagnostic tests don’t require FDA regulation, which is how the company has been able to market it so broadly.) In the meantime, they’re also working to create similar risk-profile tests for cardiovascular disease and osteoporosis and hope to have the first one, a test for heart-attack risk, ready for market within the next two years.